Abstract
Down syndrome (DS) is the most common cause of cognitive impairment associated with a congenital chromosomal abnormality, trisomy of chromosome 21. Mental retardation and congenital heart defects are key features of DS. All DS individuals develop early-onset Alzheimer’s disease-like neuropathology. Intersectin 1 gene is localized on human chromosome 21, the critical region of DS, and it has higher expression in the brain of DS patients than in normal individuals. So fully understanding functions of intersectin 1 is critical for revealing the pathogenesis of DS. Intersectin 1 protein has two isoforms: intersectin 1-L and intersectin 1-S. This review will focus on the distribution, expression characters and functions of intersectin 1 in the central nervous system.
摘要
唐氏综合征(Down syndrome, DS), 也称21 三体综合症, 由先天性染色体异常引起, 其主要特征是精神发育迟缓和先天性心脏病。 所有的DS 患者都会出现早发的阿尔茨海默病样的神经病理学特征。 Intersectin 1 基因位于人类第21 条染色体DS 的关键区域, 且Intersectin 1 蛋白在DS 病人脑中有高表达, 因此全面掌握Intersectin 1 的功能特性对进一步阐明DS的发病机制有重要意义。 Intersectin 1的功能不仅表现在中枢神经系统中特有的神经递质的传递, 并且还参与介导细胞增殖分化等有关的一系列信号通路的传导。 本文就Intersectin 1 在中枢神经系统中的分布、 表达特征及功能作一综述。
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Mafrica F, Fodale V. Opioids and Down’s syndrome. J Opioid Manag 2006, 2: 93–98.
Gardiner K, Davisson MT, Crnic LS. Building protein interaction maps for Down’s syndrome. Brief Funct Genomic Proteomic 2004, 3: 142–156.
Keating DJ, Chen C, Pritchard MA. Alzheimer’s disease and endocytic dysfunction: clues from the Down syndrome-related proteins, DSCR1 and ITSN1. Ageing Res Rev 2006, 5: 388–401.
Fernández-Chacón R, Achiriloaie M, Janz R, Albanesi JP, Südhof TC. SCAMP1 function in endocytosis. J Biol Chem 2000, 275: 12752–12756.
Ma YJ, Okamoto M, Gu F, Obata K, Matsuyama T, Desaki J, et al. Neuronal distribution of EHSH1/intersection: a molecular linker between clathrin-mediated endocytosis and signaling pathways. J Neurosci Res 2003, 71: 468–477.
Yamabhai M, Hoffman NG, Hardison NL, McPherson PS, Castagnoli L, Cesareni G, et al. Intersectin, a novel adaptor protein with two Eps15 homology and five Src homology 3 domains. J Biol Chem 1998, 273: 31401–31407.
Roos J, Kelly RB. Dap160, a neural-specific Eps15 homology and multiple SH3 domain-containing protein that interacts with Drosophila dynamin. J Biol Chem 1998, 273: 19108–19119.
Sengar AS, Wang W, Bishay J, Cohen S, Egan SE. The EH and SH3 domain Ese proteins regulate endocytosis by linking to dynamin and Eps15. EMBO J 1999, 18: 1159–1171.
Hussain NK, Jenna S, Glogauer M, Quinn CC, Wasiak S, Guipponi M, et al. Endocytic protein intersectin-1 regulates actin assembly via Cdc42 and N-WASP. Nat Cell Biol 2001, 3: 927–932.
Hurley JH, Misra S. Signaling and subcellular targeting by membrane-binding domains. Annu Rev Biophys Biomol Struct 2000, 29: 49–79.
Cataldo AM, Peterhoff CM, Troncoso JC, Gomez-Isla T, Hyman BT, Nixon RA. Endocytic pathway abnormalities precede amyloid β deposition in sporadic Alzheimer’s disease and Down syndrome: differential effects of APOE genotype and presenilin mutations. Am J Pathol 2000, 157: 277–286.
Kelly LE, Phillips AM. Molecular and genetic characterization of the interaction between the Drosophila stoned B protein and DAP-160 (intersectin). Biochem J 2005, 388(Pt 1): 195–204.
Scappini E, Koh TW, Martin NP, O’Bryan JP. Intersectin enhances huntingtin aggregation and neurodegeneration through activation of c-Jun-NH2-terminal kinase. Hum Mol Genet 2007, 16: 1862–1871.
Pucharcos C, Casas C, Nadal M, Estivill X, de la Luna S. The human intersectin genes and their spliced variants are differentially expressed. Biochim Biophys Acta 2001, 1521: 1–11.
O’Bryan JP, Mohney RP, Oldham CE. Mitogenesis and endocytosis: What’s at the intersection? Oncogene 2001, 20: 6300–6308.
Okamoto M, Schoch S, Südhof TC. EHSH1/intersectin, a protein that contains EH and SH3 domains and binds to dynamin and SNAP-25. A protein connection between exocytosis and endocytosis? J Biol Chem 1999, 274: 18446–18454.
Evergren E, Gad H, Walther K, Sundborger A, Tomilin N, Shupliakov O. Intersectin is a negative regulator of dynamin recruitment to the synaptic endocytic zone in the central synapse. J Neurosci 2007, 27: 379–390.
Malacombe M, Ceridono M, Calco V, Chasserot-Golaz S, McPherson PS, Bader MF, et al. Intersectin-1L nucleotide exchange factor regulates secretory granule exocytosis by activating Cdc42. EMBO J 2006, 25: 3494–3503.
Wang JB, Wu WJ, Cerione RA. Cdc42 and Ras cooperate to mediate cellular transformation by intersectin-L. J Biol Chem 2005, 280: 22883–22891.
McGavin MK, Badour K, Hardy LA, Kubiseski TJ, Zhang J, Siminovitch KA. The intersectin 2 adaptor links Wiskott Aldrich Syndrome protein (WASp)-mediated actin polymerization to T cell antigen receptor endocytosis. J Exp Med 2001, 194: 1777–1787.
Tong XK, Hussain NK, Adams AG, O’Bryan JP, McPherson PS. Intersectin can regulate the Ras/MAP kinase pathway independent of its role in endocytosis. J Biol Chem 2000, 275: 29894–29899.
Adams A, Thorn JM, Yamabhai M, Kay BK, O’Bryan JP. Intersectin, as adaptor protein involved in clathrin-mediated endocytosis, activates mitogenic signaling pathways. J Biol Chem 2000, 275: 27414–27420.
Mohney RP, Das M, Bivona TG, Hanes R, Adams AG, Philips MR, et al. Intersectin activates Ras but stimulates transcription through an independent pathway involving JNK. J Biol Chem 2003, 278: 47038–47045.
Martin NP, Mohney RP, Dunn S, Das M, Scappini E, O’Bryan JP. Intersectin regulates epidermal growth factor receptor endocytosis, ubiquitylation, and signaling. Mol Pharmacol 2006, 70: 1643–1653.
Verkhratsky A, Toescu EC. Neuronal-glial networks as substrate for CNS integration. J Cell Mol Med 2006, 10: 826–836.
Bessis A, Béchade C, Bernard D, Roumier A. Microglial control of neuronal death and synaptic properties. Glia 2007, 55: 233–238.
Yu Y, Chu PY, Bowser DN, Keating DJ, Dubach D, Harper I, et al. Mice deficient for the chromosome 21 ortholog Itsn1 exhibit vesicle trafficking abnormalities. Hum Mol Genet 2008, 17: 3281–3290.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ma, N., Niu, RF. & Ma, YJ. Intersectin 1: a molecular linker in the central nervous system. Neurosci. Bull. 24, 401–405 (2008). https://doi.org/10.1007/s12264-008-0715-0
Received:
Published:
Issue date:
DOI: https://doi.org/10.1007/s12264-008-0715-0